Extrahepatic bile ducts are characterized by the presence of peribiliary glands (PBGs), which represent stem cell niches implicated in biliary regeneration. Orthotopic liver transplantation may be complicated by non-anastomotic strictures (NAS) of the bile ducts, which have been associated with ischemic injury of PBGs and occur more frequently in livers obtained from donors after circulatory death than in those from brain-dead donors. The aims of the present study were to investigate the PBG phenotype in bile ducts after transplantation, the integrity of the peribiliary vascular plexus (PVP) around PBGs, and the expression of vascular endothelial growth factor-A (VEGF-A) by PBGs. Transplanted ducts obtained from patients who underwent liver transplantation were studied (N=62). Controls included explanted bile duct samples not used for transplantation (N=10) with normal histology. Samples were processed for histology, immunohistochemistry and immunofluorescence. Surface epithelium is severely injured in transplanted ducts; PBGs are diffusely damaged, particularly in ducts obtained from circulatory-dead compared to brain-dead donors. PVP is reduced in transplanted compared to controls. PBGs in transplanted ducts contain more numerous progenitor and proliferating cells compared to controls, show higher positivity for VEGF-A compared to controls, and express VEGF receptor-2. In conclusion, PBGs and associated PVP are damaged in transplanted extrahepatic bile ducts; however, an activation of the PBG niche takes place and is characterized by proliferation and VEGF-A expression. This response could have a relevant role in reconstituting biliary epithelium and vascular plexus and could be implicated in the genesis of non-anastomotic strictures.

中文翻译：

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肝移植引起的胆周腺体损伤涉及胆周血管丛和血管内皮生长因子。


肝外胆管的特征是存在胆周腺（PBG），它代表与胆道再生有关的干细胞生态位。原位肝移植可能会因胆管非吻合狭窄（NAS）而变得复杂，这与PBG的缺血性损伤有关，并且在循环死亡供体获得的肝脏中比脑死亡供体获得的肝脏更常见。本研究的目的是探讨移植后胆管中PBG的表型、PBG周围胆周血管丛（PVP）的完整性以及PBG对血管内皮生长因子-A（VEGF-A）的表达。对从接受肝移植的患者获得的移植导管进行了研究（N=62）。对照包括未用于移植的具有正常组织学的外植胆管样本（N=10）。对样品进行组织学、免疫组织化学和免疫荧光处理。移植导管表面上皮严重损伤；与脑死亡供体相比，PBG 受到广泛损坏，尤其是从循环死亡供体获得的导管中。与对照组相比，移植后的 PVP 减少。与对照相比，移植导管中的 PBG 含有更多数量的祖细胞和增殖细胞，与对照相比，VEGF-A 的阳性率更高，并表达 VEGF 受体 2。总之，移植的肝外胆管中的 PBG 和相关的 PVP 受到损害；然而，PBG 生态位发生激活，其特征是增殖和 VEGF-A 表达。这种反应可能在胆道上皮和血管丛的重建中发挥相关作用，并且可能与非吻合口狭窄的发生有关。